Rapid Computation of Thermodynamic Properties Over Multidimensional Nonbonded Parameter Spaces using Adaptive Multistate Reweighting

We show how thermodynamic properties of molecular models can be computed over a large, multidimensional parameter space by combining multistate reweighting analysis with a linear basis function approach. This approach reduces the computational cost to estimate thermodynamic properties from molecular simulations for over 130,000 tested parameter combinations from over a thousand CPU years to tens of CPU days. This speed increase is achieved primarily by computing the potential energy as a linear combination of basis functions, computed from either modified simulation code or as the difference of energy between two reference states, which can be done without any simulation code modification. The thermodynamic properties are then estimated with the Multistate Bennett Acceptance Ratio (MBAR) as a function of multiple model parameters without the need to define a priori how the states are connected by a pathway. Instead, we adaptively sample a set of points in parameter space to create mutual configuration space overlap. The existence of regions of poor configuration space overlap are detected by analyzing the eigenvalues of the sampled states' overlap matrix. The configuration space overlap to sampled states is monitored alongside the mean and maximum uncertainty to determine convergence, as neither the uncertainty or the configuration space overlap alone is a sufficient metric of convergence. This adaptive sampling scheme is demonstrated by estimating with high precision the solvation free energies of charged particles of Lennard-Jones plus Coulomb functional form. We also compute entropy, enthalpy, and radial distribution functions of unsampled parameter combinations using only the data from these sampled states and use the free energies estimates to examine the deviation of simulations from the Born approximation to the solvation free energy

Manipulating O3/P2 phase ratio in bi-phasic sodium layered oxides via ionic radius control

Funding: This work was supported by the Faraday Institution (Grant number FIRG018). The authors would like to thank Dr. David Rochester at Lancaster University for conducting the ICP-OES experiments. A.B.N. would like to acknowledge funding by the Engineering and Physical Sciences Research Council under grant numbers EP/L017008/1, EP/R023751/1, and EP/T019298/1 for the electron microscopy analysis.Bi-phasic O3/P2 sodium layered oxides have emerged as leading candidates for the commercialisation of next-generation sodium-ion batteries. However, beyond simply altering the sodium content, rational control of the O3/P2 ratio in these materials has proven particularly challenging despite being crucial for the realization of high-performance electrode materials. Here, using abundant elements, we manipulate the O3/P2 ratio using the average ionic radius of the transition metal layer and different synthesis conditions. These methods allow deterministic control over the O3/P2 ratio, even for constant Na contents. In addition, tuning the O3/P2 ratio yields high-performing materials with different performance characteristics, with a P2-rich material achieving high rate capabilities and excellent cycling stability (92% retention, 50 cycles), while an O3-rich material displayed an energy density up to 430 Wh kg−1, (85%, 50 cycles). These insights will help guide the rational design of future high-performance materials for sodium-ion batteries.Publisher PDFPeer reviewe

Full control of polarization in ferroelectric thin films using growth temperature to modulate defects

P.P. and C.W. acknowledge partial support by Swiss National Science Foundation Division II grant 200021_178782. L.R.D. acknowledges support from the US National Science Foundation under grant DMR‐1708615. L.W.M. acknowledges support from the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Materials Sciences and Engineering Division under Contract No. DE‐AC02‐05‐CH11231 (Materials Project program KC23MP) for the growth and study of defect structures in ferroic materials. A.B.N. gratefully acknowledges support from the Engineering and Physics Sciences Research Council (EPSRC) through grants EP/R023751/1 and EP/L017008/1.Deterministic control of the intrinsic polarization state of ferroelectric thin films is essential for device applications. Independently of the well-established role of electrostatic boundary conditions and epitaxial strain, the importance of growth temperature as a tool to stabilize a target polarization state during thin film growth is shown here. Full control of the intrinsic polarization orientation of PbTiO3 thin films is demonstrated-from monodomain up, through polydomain, to monodomain down as imaged by piezoresponse force microscopy-using changes in the film growth temperature. X-ray diffraction and scanning transmission electron microscopy reveal a variation of c-axis related to out-of-plane strain gradients. These measurements, supported by Ginzburg-Landau-Devonshire free energy calculations and Rutherford backscattering spectroscopy, point to a defect mediated polarization gradient initiated by a temperature dependent effective built-in field during growth, allowing polarization control not only under specific growth conditions, but ex-situ, for subsequent processing and device applications.Publisher PDFPeer reviewe

Assessing the potential impacts of a revised set of on-farm nutrient and sediment ‘basic’ control measures for reducing agricultural diffuse pollution across England

The need for improved abatement of agricultural diffuse water pollution represents cause for concern throughout the world. A critical aspect in the design of on-farm intervention programmes concerns the potential technical cost-effectiveness of packages of control measures. The European Union (EU) Water Framework Directive (WFD) calls for Programmes of Measures (PoMs) to protect freshwater environments and these comprise ‘basic’ (mandatory) and ‘supplementary’ (incentivised) options. Recent work has used measure review, elicitation of stakeholder attitudes and a process-based modelling framework to identify a new alternative set of ‘basic’ agricultural sector control measures for nutrient and sediment abatement across England. Following an initial scientific review of 708 measures, 90 were identified for further consideration at an industry workshop and 63 had industry support. Optimisation modelling was undertaken to identify a shortlist of measures using the Demonstration Test Catchments as sentinel agricultural landscapes. Optimisation selected 12 measures relevant to livestock or arable systems. Model simulations of 95% implementation of these 12 candidate ‘basic’ measures, in addition to business-as-usual, suggested reductions in the national agricultural nitrate load of 2.5%, whilst corresponding reductions in phosphorus and sediment were 11.9% and 5.6%, respectively. The total cost of applying the candidate ‘basic’ measures across the whole of England was estimated to be £450 million per annum, which is equivalent to £52 per hectare of agricultural land. This work contributed to a public consultation in 2016

The pediatric glucocorticoid toxicity index

Objectives: To develop a Pediatric glucocorticoid toxicity index (pGTI), a standardized, weighted clinical outcome assessment that measures change in glucocorticoid (GC) toxicity over time. Methods: Fourteen physician experts from 7 subspecialties participated. The physician experts represented multiple subspecialties in which GCs play a major role in the treatment of inflammatory disease: nephrology, rheumatology, oncology, endocrinology, genetics, psychiatry, and maternal-fetal medicine. Nine investigators were from Canada, Europe, or New Zealand, and 5 were from the United States. Group consensus methods and multi-criteria decision analysis were used. The pGTI is an aggregate assessment of GC toxicities that are common, important, and dynamic. These toxicities are organized into health domains graded as minor, moderate, or major and are weighted according to severity. The relative weights were derived by group consensus and multi-criteria decision analysis using the 1000MindsTM software platform. Two quantitative scores comprise the overall toxicity profile derived from pGTI data: (1) the Cumulative Worsening Score; and (2) the Aggregate Improvement Score. The pGTI also includes a qualitative, unweighted record of GC side-effects known as the Damage Checklist, which documents less common toxicities that, although potentially severe, are unlikely to change with varying GC dosing. Results: One hundred and seven (107) toxicity items were included in the pGTI and thirty-two (32) in the Damage Checklist. To assess the degree to which the pGTI corresponds to expert clinical judgement, the investigators ranked 15 cases by clinical judgement from highest to lowest GC toxicity. Expert rankings were then compared to case ranking by the pGTI, yielding excellent agreement (weighted kappa 0.86). The pGTI was migrated to a digital environment following its development and initial validation. The digital platform is designed to ensure ease-of-use in the clinic, rigor in application, and accuracy of scoring. Clinic staff enter vital signs, laboratory results, and medication changes relevant to pGTI scoring. Clinicians record findings for GC myopathy, skin toxicity, mood dysfunction, and infection. The pGTI algorithms then apply the weights to these raw data and calculate scores. Embedded logic accounts for the impact of age- and sex-related reference ranges on several health domains: blood pressure, lipid metabolism, and bone mineral density. Other algorithms account for anticipated changes in the height Z-scores used in the growth domain, thereby addressing a concern unique to GC toxicity in children. The Damage Checklist ensures comprehensive measurement of GC toxicity but does not contribute to pGTI scoring, because the scored domains emphasize manifestations of GC toxicity that are likely to change over the course of a trial. Conclusions: We describe the development and initial evaluation of a weighted, composite toxicity index for the assessment of morbidity related to GC use in children and adolescents. Developing the pGTI digital platform was essential for performing the nuanced calculations necessary to ensure rigor, accuracy, and ease-of-use in both clinic and research settings

Direct observations of the effect of fine sediment deposition on the vertical movement of Gammarus pulex (Amphipoda: Gammaridae) during substratum drying

Benthic macroinvertebrates inhabit the streambed sediments of temporary streams during drying events. Fine sediment (< 2 mm in diameter) deposition and clogging of interstitial pathways reduces the connectivity between benthic and subsurface habitats, potentially inhibiting macroinvertebrate vertical movements. Direct observations within subsurface sediments are, however, inherently difficult. As a result, confirmation of macroinvertebrate vertical movement, and the effect of fine sediment, is limited. We used laboratory mesocosms containing transparent gravel sized particles (10–15 mm) to facilitate the direct observation and tracking of vertical movements by Gammarus pulex in response to water level reduction and sedimentation. Seven sediment treatments comprised two fine sediment fractions (small: 0.125–0.5 mm, coarse sand: 0.5–1 mm) deposited onto the surface of the substrate, and a control treatment where no fine sediment was applied. We found that G. pulex moved into the subsurface gravel sediments in response to drying, but their ability to remain submerged during water level reduction was impeded by fine sediment deposition. In particular deposition of the coarser sand fraction clogged the sediment surface, limiting vertical movements. Our results highlight the potential effect of sedimentation on G. pulex resistance to drying events in streams

Physicochemical conditions and timing of rodingite formation: evidence from rodingite-hosted fluid inclusions in the JM Asbestos mine, Asbestos, Québec

Fluid inclusions and geological relationships indicate that rodingite formation in the Asbestos ophiolite, Québec, occurred in two, or possibly three, separate episodes during thrusting of the ophiolite onto the Laurentian margin, and that it involved three fluids. The first episode of rodingitization, which affected diorite, occurred at temperatures of between 290 and 360°C and pressures of 2.5 to 4.5 kbar, and the second episode, which affected granite and slate, occurred at temperatures of between 325 and 400°C and pressures less than 3 kbar. The fluids responsible for these episodes of alteration were moderately to strongly saline (~1.5 to 6.3 m eq. NaCl), rich in divalent cations and contained appreciable methane. A possible third episode of alteration is suggested by primary fluid inclusions in vesuvianite-rich bodies and secondary inclusions in other types of rodingite, with significantly lower trapping temperatures, salinity and methane content. The association of the aqueous fluids with hydrocarbon-rich fluids containing CH4 and higher order alkanes, but no CO2, suggests strongly that the former originated from the serpentinites. The similarities in the composition of the fluids in all rock types indicate that the ophiolite had already been thrust onto the slates when rodingitization occurred

2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative

Objective The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease—this being the appropriate current paradigm underlying the disease construct “rheumatoid arthritis.” Results In the new criteria set, classification as “definite RA” is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0–5), serologic abnormality (score range 0–3), elevated acute-phase response (score range 0–1), and symptom duration (2 levels; range 0–1). Conclusion This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct “rheumatoid arthritis.”Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78045/1/27584_ftp.pd